HAE
MCID: HRD002
MIFTS: 60

Hereditary Angioedema (HAE)

Categories: Bone diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Oral diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hereditary Angioedema

MalaCards integrated aliases for Hereditary Angioedema:

Name: Hereditary Angioedema 12 74 52 25 58 36 15
Hereditary Angioneurotic Edema 12 52 25 58
Hane 12 52 25
Hae 52 25 58
Angioedemas, Hereditary 43 71
Angioedema, Hereditary 52 54
Hereditary C1 Esterase Inhibitor Deficiency - Deficient Factor 71
Hereditary Non Histamine-Induced Angioedema 58
Hereditary Bradykinine-Induced Angioedema 58
Hereditary Angioedema Types I and Ii 71
Deficiency of C1 Esterase Inhibitor 52
C1 Esterase Inhibitor Deficiency 25
Hereditary Angioedema Type 1 52
Familial Angioneurotic Edema 58
C1 Inhibitor Deficiency 25

Characteristics:

Orphanet epidemiological data:

58
hereditary angioedema
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe),1-9/100000 (Denmark),1-9/100000 (Norway),1-9/100000 (Spain); Age of onset: All ages;

Classifications:

Orphanet: 58  
Rare systemic and rhumatological diseases
Rare allergic disease


External Ids:

Disease Ontology 12 DOID:14735
KEGG 36 H01006
MeSH 43 D054179
NCIt 49 C84758
SNOMED-CT 67 82966003
ICD10 via Orphanet 33 D84.1
UMLS via Orphanet 72 C0019243
Orphanet 58 ORPHA91378
UMLS 71 C0019243 C0398775 C2717905

Summaries for Hereditary Angioedema

NIH Rare Diseases : 52 Hereditary angioedema (HAE) is a disease characterized by recurrent episodes (also called attacks) of severe swelling of the skin and mucous membranes. The age at which attacks begin varies, but most people have their first one in childhood or adolescence. The frequency of attacks usually increases after puberty. Attacks most often affect 3 parts of the body: Skin - the most common sites are the face (such as the lips and eyes), hands, arms, legs, genitals, and buttocks. Skin swelling can cause pain, dysfunction, and disfigurement, although it is generally not dangerous and is temporary. Gastrointestinal tract - the stomach, intestines, bladder, and/or urethra may be involved. This may cause symptoms such as nausea, vomiting, diarrhea, and abdominal pain. Upper airway (such as the larynx and tongue) - this can cause upper airway obstruction and may be life-threatening. The majority of attacks affecting the airway resolve before complete airway obstruction. Attacks may involve one area of the body at a time, or they may involve a combination of areas. They always go away on their own but last from 2 to 4 days. While people with HAE have reported various triggers of attacks, emotional stress, physical stress, and dental procedures are the most commonly reported triggers. There are several types of HAE. Types I and II are caused by mutations in the C1NH gene (also called the SERPING1 gene ), which provides instructions for making the C1 inhibitor protein . Type I is due to deficiency of C1 inhibitor, and type II is due to dysfunction of C1 inhibitor. These types are also characterized by abnormal complement protein levels . Inheritance of types I and II is autosomal dominant , but not all people with a SERPING1 gene mutation will develop symptoms of HAE. A third type is called HAE with normal C1 inhibitor. This type is characterized by normal C1 inhibitor and normal complement protein levels, and usually begins in adulthood. While some cases of type III are due to mutations in the F12 gene , in other cases the cause is not yet known. The inheritance of this form is also thought to be autosomal dominant. Management of HAE involves treatment of sudden (acute) attacks and preventing attacks (prophylaxis ). Treatment for acute attacks in types I and II includes replacement with C1 inhibitor concentrates, a kallikrein inhibitor , or fresh-frozen plasma (by infusion). Sudden attacks involving the upper airway may involve intubation if stridor or signs of respiratory distress are present. HAE with normal C1 inhibitor levels is treated similarly, however C1 inhibitor infusion is not effective. Prophylaxis may involve regular injections of C1 inhibitor concentrates, long-term androgen (male hormone ) therapy, or antifibrinolytics . The long-term outlook varies depending on the frequency and location of attacks, and the severity of attacks in each person. Attacks generally continue throughout life, but the frequency of attacks can be significantly reduced with therapy.

MalaCards based summary : Hereditary Angioedema, also known as hereditary angioneurotic edema, is related to angioedema, hereditary, type i and hereditary angioedema with normal c1inh. An important gene associated with Hereditary Angioedema is F12 (Coagulation Factor XII), and among its related pathways/superpathways are Complement and coagulation cascades and Response to elevated platelet cytosolic Ca2+. The drugs Ciprofloxacin and Vancomycin have been mentioned in the context of this disorder. Affiliated tissues include skin, tongue and eye, and related phenotypes are angioedema and ascites

Genetics Home Reference : 25 Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack. Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family. There are three types of hereditary angioedema, called types I, II, and III, which can be distinguished by their underlying causes and levels of a protein called C1 inhibitor in the blood. The different types have similar signs and symptoms. Type III was originally thought to occur only in women, but families with affected males have been identified.

KEGG : 36 Hereditary angioedema (HAE) is a rare genetic disorder, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tract or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result from deficiency of the plasma protease inhibitor, C1 inhibitor (C1INH). Type I HAE is caused by decreased expression of C1INH in the plasma whereas type 2 HAE, consisting approximately 15% of patients with HAE, is due to expression of a dysfunctional C1INH protein. HAE type III has been observed exclusively in women and appears to be correlated with high estrogen levels.

Wikipedia : 74 Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The... more...

Related Diseases for Hereditary Angioedema

Diseases in the Angioedema family:

Angioedema, Hereditary, Type I Angioedema, Hereditary, Type Iii
Hereditary Angioedema Acquired Angioedema
Acquired Angioedema Type 1 Acquired Angioedema Type 2

Diseases related to Hereditary Angioedema via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 282)
# Related Disease Score Top Affiliating Genes
1 angioedema, hereditary, type i 34.4 SERPING1 PLG F12
2 hereditary angioedema with normal c1inh 33.0 SERPINA1 PLG KRT1 KNG1 ELANE CPN1
3 c1 inhibitor deficiency 32.3 SERPING1 KNG1 KLKB1 F12 C1S BDKRB2
4 acquired angioedema 31.5 SERPING1 C1S
5 urticaria 31.4 SERPING1 F12 CPN1 C1S
6 hydrops, lactic acidosis, and sideroblastic anemia 31.1 SERPING1 KNG1 C1S
7 melkersson-rosenthal syndrome 30.6 SERPING1 ACE
8 allergic urticaria 30.5 SERPING1 KNG1
9 capillary leak syndrome 30.5 SERPING1 ELANE C4A C1S
10 angioedema 30.0 XPNPEP2 SERPING1 SERPINA1 PLG MASP2 KNG1
11 mannose-binding lectin deficiency 30.0 MBL2 MASP2
12 complement component 2 deficiency 30.0 SERPINA1 C4B C4A
13 vasculitis 29.7 SERPINA1 MBL2 ELANE C1S
14 iga glomerulonephritis 29.6 MBL2 MASP1 ACE
15 lipoprotein quantitative trait locus 29.6 PLG KNG1 ANGPT1 ACE
16 complement deficiency 29.5 SERPING1 MBL2 C4B C4A C1S
17 adult respiratory distress syndrome 29.4 ELANE C4A ANGPT1 ACE
18 glomerulonephritis 29.2 MBL2 MASP1 ELANE C4B C4A C1S
19 hypertension, essential 28.6 PLG KNG1 KLKB1 KLK1 F12 BDKRB2
20 angioedema, hereditary, type iii 12.5
21 hereditary angioedema with c1inh deficiency 12.4
22 plg-related hereditary angioedema with normal c1inh 12.3
23 angpt1-related hereditary angioedema with normal c1inh 12.3
24 angioedema induced by ace inhibitors 11.5
25 acquired angioedema with c1inh deficiency 11.5
26 frasier syndrome 11.3
27 complement component 4, partial deficiency of 11.0
28 pseudomembranous conjunctivitis 10.5 SERPING1 PLG
29 acute anterolateral myocardial infarction 10.5 PLG ACE
30 cholinergic urticaria 10.5 SERPING1 KNG1
31 ligneous conjunctivitis 10.5 PLG ELANE
32 cholesterol embolism 10.5 PLG ACE
33 intracranial embolism 10.4 PLG ACE
34 physical urticaria 10.4 SERPING1 KNG1
35 autoimmune lymphoproliferative syndrome, type v 10.4
36 fibromuscular dysplasia 10.4 SERPINA1 ACE
37 autoimmune disease 10.4
38 constrictive pericarditis 10.4 SERPINA1 ACE
39 louse-borne relapsing fever 10.4 SERPING1 C4B
40 diffuse scleroderma 10.4 KNG1 ACE
41 acute pancreatitis 10.3
42 pancreatitis 10.3
43 acute mountain sickness 10.3 BDKRB2 ACE
44 hypertension, diastolic 10.3
45 osteoarthritis 10.3
46 trypanosomiasis 10.3 KNG1 BDKRB2 ACE
47 alpha-2-plasmin inhibitor deficiency 10.3 SERPING1 PLG
48 exanthem 10.3
49 diarrhea 10.3
50 lupus erythematosus 10.3

Graphical network of the top 20 diseases related to Hereditary Angioedema:



Diseases related to Hereditary Angioedema

Symptoms & Phenotypes for Hereditary Angioedema

Human phenotypes related to Hereditary Angioedema:

58 31 (show all 8)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 angioedema 58 31 hallmark (90%) Very frequent (99-80%) HP:0100665
2 ascites 58 31 occasional (7.5%) Occasional (29-5%) HP:0001541
3 abdominal pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0002027
4 intestinal obstruction 58 31 occasional (7.5%) Occasional (29-5%) HP:0005214
5 facial edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0000282
6 intestinal edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0005225
7 laryngeal edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0012027
8 edema 58 Very frequent (99-80%)

GenomeRNAi Phenotypes related to Hereditary Angioedema according to GeneCards Suite gene sharing:

26 (show all 31)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-107 10.03 MBL2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-113 10.03 C4A C4B
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.03 C4A C4B
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-137 10.03 C4A C4B
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-19 10.03 C4A C4B
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.03 C4A C4B
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-52 10.03 MBL2
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-98 10.03 C4A C4B SERPING1
9 Decreased viability GR00106-A-0 9.8 MBL2
10 Decreased viability GR00249-S 9.8 ANGPT1 BDKRB2 F12 KLKB1 SERPING1
11 Decreased viability GR00381-A-1 9.8 BDKRB2 F12 KLKB1
12 Decreased viability GR00381-A-3 9.8 BDKRB2
13 Decreased viability GR00386-A-1 9.8 ANGPT1
14 Decreased viability GR00402-S-2 9.8 ANGPT1 C4B F12
15 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.72 KLK1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.72 C4A C4B SERPING1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.72 C4A C4B
18 Increased shRNA abundance (Z-score > 2) GR00366-A-167 9.72 KLK1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.72 KLK1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.72 KLK1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.72 KLK1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-216 9.72 SERPING1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.72 SERPING1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.72 SERPING1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.72 C4A C4B SERPING1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-45 9.72 SERPING1
27 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.72 KLK1 SERPING1
28 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.72 SERPING1
29 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.72 C4A C4B
30 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.72 KLK1
31 Increased shRNA abundance (Z-score > 2) GR00366-A-8 9.72 C4A C4B

MGI Mouse Phenotypes related to Hereditary Angioedema:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.4 ACE ANGPT1 BDKRB2 C4B ELANE F12

Drugs & Therapeutics for Hereditary Angioedema

Drugs for Hereditary Angioedema (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 79)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ciprofloxacin Approved, Investigational Phase 4 85721-33-1 2764
2
Vancomycin Approved Phase 4 1404-90-6 14969 441141
3
Metronidazole Approved Phase 4 443-48-1 4173
4
Omalizumab Approved, Investigational Phase 4 242138-07-4
5
Lactitol Approved, Investigational Phase 4 585-88-6, 585-86-4 493591
6
Bradykinin Investigational Phase 4 58-82-2 439201
7 Anti-Infective Agents Phase 4
8 Cytochrome P-450 Enzyme Inhibitors Phase 4
9 Anti-Bacterial Agents Phase 4
10 Antiparasitic Agents Phase 4
11 Antiprotozoal Agents Phase 4
12 Antibiotics, Antitubercular Phase 4
13 Kininogens Phase 4
14 Bradykinin Receptor Antagonists Phase 4
15 Respiratory System Agents Phase 4
16 Anti-Allergic Agents Phase 4
17 Anti-Asthmatic Agents Phase 4
18 Immunoglobulins Phase 4
19 Antibodies Phase 4
20 Immunosuppressive Agents Phase 4
21 Immunoglobulins, Intravenous Phase 4
22 Rho(D) Immune Globulin Phase 4
23 gamma-Globulins Phase 4
24
Histidine Investigational, Nutraceutical Phase 4 71-00-1 6274
25
Icatibant Approved, Investigational Phase 3 138614-30-9, 130308-48-4 71364
26
tannic acid Approved Phase 3 1401-55-4
27
Benzocaine Approved, Investigational Phase 3 94-09-7, 1994-09-7 2337
28
Tranexamic Acid Approved Phase 3 1197-18-8 5526
29 Antibodies, Monoclonal Phase 3
30 Passionflower Phase 3
31 Fibrinolytic Agents Phase 3
32 Hemostatics Phase 3
33 Antifibrinolytic Agents Phase 3
34 Coagulants Phase 3
35 Pharmaceutical Solutions Phase 3
36
Danazol Approved Phase 2 17230-88-5 28417
37
Cortisone Experimental Phase 2 53-06-5 222786
38 Hormones Phase 2
39 Hormone Antagonists Phase 2
40 Estrogen Antagonists Phase 2
41 Estrogen Receptor Antagonists Phase 2
42 Estrogen Receptor Modulators Phase 2
43 Estrogens Phase 2
44 Angiotensin-Converting Enzyme Inhibitors Phase 2
45 Plasminogen Phase 2
46 Kallikreins Phase 2
47
Digoxin Approved Phase 1 20830-75-5 30322 2724385
48
Clotrimazole Approved, Vet_approved Phase 1 23593-75-1 2812
49
Miconazole Approved, Investigational, Vet_approved Phase 1 22916-47-8 4189
50
Midazolam Approved, Illicit Phase 1 59467-70-8 4192

Interventional clinical trials:

(show top 50) (show all 103)
# Name Status NCT ID Phase Drugs
1 Effect of Intravenous Administration of C1-inhibitor on Inflammation and Coagulation After Bronchial Instillation of House Dust Mite Allergen and Lipopolysaccharide in Allergic Asthma Patients Unknown status NCT03051698 Phase 4 C1-inhibitor;Antibiotics
2 Prospective Open-label Uncontrolled Multi-center Post-marketing Study to Assess Inhibitory Antibody Formation in Subjects With Congenital C1-INH Deficiency and Acute Hereditary Angioedema (HAE) Attacks Treated With Berinert® , a C1-esterase Inhibitor Completed NCT01467947 Phase 4
3 Hereditary Angioedema : Interest From the Use of a Call Center During the Attacks. Completed NCT01679912 Phase 4
4 Open Label, Multicenter Study to Evaluate Efficacy, Safety and Tolerability of a Self-Administered Subcutaneous Formulation of Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema (IHA) Completed NCT01457430 Phase 4 Icatibant
5 A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks Completed NCT00914966 Phase 4
6 A Phase IV, Randomized, Double-Blind, Placebo-Controlled Exploratory Study of Xolair (Omalizumab) for Treatment of Idiopathic Angioedema in Patients Who Remain Symptomatic Despite Current Therapy Completed NCT02966314 Phase 4 Omalizumab;Placebos
7 A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions Recruiting NCT03576469 Phase 4
8 Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Determine the Efficacy of 1000u, and 1500u of C1-INH Compared to Placebo at the Time of Prodromal Symptoms in Preventing an Acute HAE Exacerbation. Withdrawn NCT01151735 Phase 4 C-1-esterase;C-1-esterase;placebo
9 A Double-blind, Randomized, Placebo-controlled, Cross-over Study to Evaluate the Clinical Efficacy and Safety of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema Completed NCT01912456 Phase 3
10 An Open-label, Randomized Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema Completed NCT02316353 Phase 3
11 Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks Completed NCT00168103 Phase 2, Phase 3
12 Randomized, Double Blind, Placebo-Controlled, Multicenter Study of a Subcutaneous Formulation of Icatibant for the Treatment of Hereditary Angioedema Completed NCT00097695 Phase 3 Icatibant;Placebo
13 An Open-Label Study of Icatibant in Japanese Subjects With Acute Attacks of Hereditary Angioedema. Completed NCT03888755 Phase 3 Icatibant
14 LEVP2006-4 CHANGE 3 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Use of C1INH-nf (Human) for the Prophylactic Treatment to Prevent HAE Attacks and as Treatment in Acute HAE Attacks Completed NCT00462709 Phase 3
15 A Phase II/III Study of the Efficacy and Safety of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema Completed NCT00262288 Phase 2, Phase 3 i.v. recombinant human C1 inhibitor
16 A Randomized, Placebo-controlled, Double-blind Phase III Study of the Efficacy and Safety of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema Completed NCT00262301 Phase 3 recombinant human C1 inhibitor;Placebo
17 A Randomized, Placebo-controlled, Double Blind Phase II/III Study of the Safety and Efficacy of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema Completed NCT00225147 Phase 2, Phase 3 Recombinant Human C1 Inhibitor;placebo
18 OPuS-2: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX4161 for 12 Weeks as an Oral Prophylaxis Treatment for Attacks of Hereditary Angioedema Completed NCT02303626 Phase 2, Phase 3 BCX4161;Placebo
19 A Double-blind, Placebo-controlled Study (72 Patients, Randomized 1:1) Followed by a Repeat-dosing Phase to Assess the Efficacy and Safety of DX-88 (Ecallantide; Recombinant Plasma Kallikrein Inhibitor) for the Treatment of Acute Attacks of Hereditary Angioedema Completed NCT00262080 Phase 3 ecallantide;Phosphate Buffer Saline (PBS),
20 A Phase 3, Open-label, Single-period Study to Evaluate the Safety and Treatment Effect of Intravenous Administration of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE) Completed NCT02865720 Phase 3 CINRYZE 500 U;CINRYZE 1000 U
21 A Phase 3, Randomized, Double-blind, Placebo-controlled, Two-period, Three-sequence, Partial Crossover Study to Evaluate the Efficacy and Safety of Subcutaneous Administration of 2000 IU of C1 Esterase Inhibitor [Human] Liquid for Injection for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema Completed NCT02584959 Phase 3 C1 esterase inhibitor [human] liquid;Placebo
22 LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks Completed NCT00438815 Phase 3
23 A Phase 3, Multicenter, Randomized, Single-Blind, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Intravenous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Prevention of Angioedema Attacks in Children 6 to 11 Years of Age With Hereditary Angioedema Completed NCT02052141 Phase 3
24 Open-label Extension Study of CE1145 (Human Pasteurized C1 Esterase Inhibitor Concentrate) in Subjects With Congenital C1-INH Deficiency and Acute HAE Attacks Completed NCT00292981 Phase 3 C1 Esterase Inhibitor
25 EDEMA4: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of DX-88 (Ecallantide) for the Treatment of Acute Attacks of Hereditary Angioedema Completed NCT00457015 Phase 3 ecallantide;Phosphate Buffer Saline (PBS), pH 7.0
26 Open-label Patient Continuation of DX-88 (Ecallantide) for Acute Hereditary Angioedema Attacks Completed NCT00456508 Phase 3 ecallantide
27 Pharmacokinetics Berinert P Study of Subcutaneous Versus Intravenous Administration in Subjects With Moderate Hereditary Angioedema - The Passion Study Completed NCT00748202 Phase 3 C1-Esterase Inhibitor
28 HELP Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate DX-2930 For Long-Term Prophylaxis Against Acute Attacks of Hereditary Angioedema (HAE) Completed NCT02586805 Phase 3 DX-2930 - 300mg/2wk;DX-2930 - 300mg/4wk;DX-2930 - 150mg/4wk;Placebo
29 Open Label, Multicenter Study to Evaluate Safety, Local Tolerability, Convenience, and Efficacy of a Self-Administered Subcutaneous Formulation of Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema Completed NCT00997204 Phase 3 Icatibant
30 HELP Study ExtensionTM: An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of DX-2930 for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) Completed NCT02741596 Phase 3 DX-2930;DX-2930
31 LEVP2005-1/Part B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE Attacks Completed NCT01005888 Phase 3 Placebo (saline)
32 Randomised Double Blind, Controlled, Parallel Group, Multicentre Study of a Subcutaneous Formulation of Icatibant Versus Oral Tranexamic Acid for the Treatment of Hereditary Angioedema (HAE) Completed NCT00500656 Phase 3 Icatibant;Tranexamic Acid;Oral Placebo;S.C. Placebo
33 A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks of Angioedema in Patients With HAE Completed NCT01188564 Phase 3 rhC1INH;Placebo (Saline)
34 A Phase III Randomized, Double-Blind,Placebo-Controlled, Multicenter Study of Icatibant for Subcutaneous Injection in Patients With Acute Attacks of Hereditary Angioedema (HAE) Completed NCT00912093 Phase 3 Icatibant;Placebo
35 A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents With Hereditary Angioedema Completed NCT01386658 Phase 3 icatibant
36 LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks Completed NCT00289211 Phase 3 Placebo (saline)
37 Pharmacokinetics, Clinical Efficacy and Safety of C1 Inhibitor Concentrate (C1-Esteraseremmer-N) for the Treatment of Hereditary (and Acquired) Angioedema Completed NCT00125151 Phase 3 C1 inhibitor concentrate (C1-esteraseremmer-N)
38 Pharmacokinetics, Clinical Efficacy and Safety of C1 Inhibitor Concentrate (C1-Esteraseremmer-N) for the Treatment of Hereditary (and Acquired) Angioedema Completed NCT00125541 Phase 2, Phase 3 C1 inhibitor concentrate (C1-esteraseremmer-N)
39 An Open-label Study to Evaluate the Long-term Safety of Daily Oral BCX7353 in Subjects With Type I and II Hereditary Angioedema Recruiting NCT03472040 Phase 2, Phase 3 BCX7353
40 A Phase 3 Multi-center, Open-label Study to Evaluate the Efficacy and Safety of Lanadelumab (SHP643) in Japanese Subjects With Hereditary Angioedema Recruiting NCT04180163 Phase 3 Lanadelumab
41 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX7353 as an Oral Treatment for the Prevention of Attacks in Subjects With Hereditary Angioedema Active, not recruiting NCT03485911 Phase 3 BCX7353 capsules;Placebo oral capsule
42 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX7353 as an Oral Treatment for the Prevention of Attacks in Subjects With Hereditary Angioedema Active, not recruiting NCT03873116 Phase 3 BCX7353 capsules;BCX7353 capsules;Placebo oral capsule
43 SPRING STUDY: An Open-Label, Multicenter, Phase 3 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects 2 to <12 Years of Age Active, not recruiting NCT04070326 Phase 3 Lanadelumab
44 A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH) and Acquired Angioedema (AAE) Due to C1-INH Deficiency Active, not recruiting NCT04206605 Phase 3 Lanadelumab
45 OPuS-4: An Open-label Study to Evaluate the Long-term Safety of Avoralstat in Subjects With Hereditary Angioedema Terminated NCT02670720 Phase 3 avoralstat
46 A 3-Part Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Subcutaneous Ecallantide in Prepubertal Paediatric Patients Experiencing Acute Attacks of Hereditary Angioedema (HAE) Withdrawn NCT01253382 Phase 2, Phase 3
47 A Multicenter, Open-Label Study to Assess the Tolerability and Safety of a Single, Subcutaneous Administration of Ecallantide in Children and Adolescents With Hereditary Angioedema Unknown status NCT01832896 Phase 2 Ecallantide subcutaneous dosing
48 An Open-label, Cross-over, Dose-ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of the Subcutaneous Administration of a Human Plasma-derived C1-esterase Inhibitor in Subjects With Hereditary Angioedema Completed NCT01576523 Phase 1, Phase 2
49 Pharmacokinetics, Clinical Efficacy and Safety of C1 Inhibitor Concentrate (C1-Esteraseremmer-N) for the Treatment of Hereditary (and Acquired) Angioedema Completed NCT00119431 Phase 2 C1 inhibitor concentrate
50 An Open-label Exploratory Phase II Study of the Safety and Immunogenicity of Repeated "rhC1INH" Administration of 50 U/Kg in Patients With Hereditary C1 Inhibitor Deficiency ("HAE") Completed NCT00851409 Phase 2 Recombinant Human C1 Inhibitor

Search NIH Clinical Center for Hereditary Angioedema

Inferred drug relations via UMLS 71 / NDF-RT 50 :


C1 esterase inhibitor (human)

Cochrane evidence based reviews: angioedemas, hereditary

Genetic Tests for Hereditary Angioedema

Anatomical Context for Hereditary Angioedema

MalaCards organs/tissues related to Hereditary Angioedema:

40
Skin, Tongue, Eye, Testes, Endothelial, Liver, Bone

Publications for Hereditary Angioedema

Articles related to Hereditary Angioedema:

(show top 50) (show all 2276)
# Title Authors PMID Year
1
Nonsense mutations affect C1 inhibitor messenger RNA levels in patients with type I hereditary angioneurotic edema. 61 54 6
1885769 1991
2
De novo homozygous mutation of the C1 inhibitor gene in a patient with hereditary angioedema. 61 6
23688413 2013
3
International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. 6 61
22197274 2012
4
Gonadal mosaicism in hereditary angioedema. 61 6
16813612 2006
5
Type I C1 inhibitor deficiency with a small messenger RNA resulting from deletion of one exon. 61 6
2723063 1989
6
Restriction fragment length polymorphism of the C1 inhibitor gene in hereditary angioneurotic edema. 6 61
2890659 1987
7
Altered C1 inhibitor genes in type I hereditary angioedema. 61 6
3587308 1987
8
A new case of homozygous C1-inhibitor deficiency suggests a role for Arg378 in the control of kinin pathway activation. 6
20864152 2010
9
First case of homozygous C1 inhibitor deficiency. 6
17137866 2006
10
Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. 6
8755917 1996
11
A single base deletion from the C1-inhibitor gene causes type I hereditary angio-oedema. 6
1339401 1992
12
An RNA splice site mutation in the C1-inhibitor gene causes type I hereditary angio-oedema. 6
1684567 1991
13
Perioperative management of a patient with hereditary angioedema during off-pump coronary artery bypass graft surgery. 54 61
20522360 2010
14
[Emergency management of acute angioedema]. 54 61
20461661 2010
15
Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant. 54 61
19758369 2010
16
The bradykinin-forming cascade and its role in hereditary angioedema. 61 54
20377108 2010
17
Advances in basic and clinical immunology in 2009. 54 61
20226292 2010
18
Novel and recurrent mutations in the C1NH gene of Arab patients affected with hereditary angioedema. 54 61
19752569 2010
19
Peri-operative management of a patient with hereditary angioedema undergoing laparoscopic cholecystectomy. 54 61
19849675 2010
20
Clinical review of hereditary angioedema: diagnosis and management. 61 54
19940422 2009
21
Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. 54 61
19767078 2009
22
Kallikrein-kinin system and fibrinolysis in hereditary angioedema due to factor XII gene mutation Thr309Lys. 54 61
19474702 2009
23
Modern preoperative and intraoperative management of hereditary angioedema. 54 61
19368763 2009
24
When is prophylaxis for hereditary angioedema necessary? 61 54
19492656 2009
25
Advances in basic and clinical immunology in 2008. 54 61
19203657 2009
26
Hereditary angioedema: new hopes for an orphan disease. 61 54
19160940 2008
27
[67-year-old patient with speech disorder and dysphagia]. 61 54
19006046 2008
28
Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma. 54 61
18814451 2008
29
Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. 61 54
18586324 2008
30
Successful resolution of bowel obstruction in a patient with hereditary angioedema. 61 54
18467921 2008
31
The spectrum and treatment of angioedema. 61 54
18374684 2008
32
Hereditary angioedema and pregnancy: a successful outcome using C1 esterase inhibitor concentrate. 54 61
18337530 2008
33
Biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s. 54 61
18242991 2008
34
Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P. 61 54
18158172 2008
35
New mutations in C1 esterase inhibitor (SERPING1) in a German family with hereditary angioedema. 61 54
20306692 2008
36
Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. 61 54
18758157 2008
37
Possible disease-modifying factors: the mannan-binding lectin pathway and infections in hereditary angioedema of children and adults. 61 54
18250972 2008
38
Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. 54 61
18220146 2008
39
Anti-cholesterol antibody levels in hereditary angioedema. 61 54
18205707 2007
40
Established and new treatments for hereditary angioedema: An update. 54 61
17768103 2007
41
Hereditary angioedema: a Taiwanese family with a novel gene mutation. 61 54
18035804 2007
42
Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). 61 54
17418383 2007
43
Relationship between copy number of genes (C4A, C4B) encoding the fourth component of complement and the clinical course of hereditary angioedema (HAE). 61 54
17229465 2007
44
Hereditary angioedema associated with heterozygous factor V Leiden mutation in a patient with Purpura fulminans. 54 61
17068406 2007
45
Laboratory testing for C1 inhibitor deficiency: a comparison of two approaches to C1 inhibitor function. 61 54
17270096 2007
46
Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. 61 54
17073887 2006
47
Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. 54 61
17186468 2006
48
Pregnancy and C1 esterase inhibitor deficiency: a successful outcome. 54 61
16783582 2006
49
Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. 54 61
16638441 2006
50
[Hereditary angioedema. A report of a case and literature review]. 54 61
16634360 2006

Variations for Hereditary Angioedema

ClinVar genetic disease variations for Hereditary Angioedema:

6 (show all 18) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLG NM_000301.3(PLG):c.988A>G (p.Lys330Glu)SNV Pathogenic 590291 rs889957249 6:161139762-161139762 6:160718730-160718730
2 F12 NM_000505.4(F12):c.983C>A (p.Thr328Lys)SNV Pathogenic 1169 rs118204456 5:176831232-176831232 5:177404231-177404231
3 SERPING1 NM_000062.2(SERPING1):c.-99dupduplication Likely benign 305009 rs28362939 11:57365111-57365112 11:57597638-57597639
4 F12 NM_000505.3(F12):c.-57G>CSNV Likely benign 369462 rs41309132 5:176836585-176836585 5:177409584-177409584
5 F12 NM_000505.3(F12):c.-62C>TSNV Likely benign 369463 rs187018744 5:176836590-176836590 5:177409589-177409589
6 F12 , SLC34A1 NM_000505.3(F12):c.1251-7C>TSNV Likely benign 352989 rs375340260 5:176830625-176830625 5:177403624-177403624
7 F12 , SLC34A1 NM_003052.5(SLC34A1):c.1702C>T (p.His568Tyr)SNV Benign/Likely benign 352975 rs34225933 5:176825069-176825069 5:177398068-177398068
8 F12 , SLC34A1 NM_003052.5(SLC34A1):c.*179G>ASNV Benign/Likely benign 352979 rs141664220 5:176825466-176825466 5:177398465-177398465
9 F12 , SLC34A1 NM_003052.5(SLC34A1):c.*485G>ASNV Benign/Likely benign 352985 rs143160780 5:176825772-176825772 5:177398771-177398771
10 F12 , SLC34A1 NM_000505.3(F12):c.1342C>T (p.Arg448Cys)SNV Benign/Likely benign 352986 rs115119084 5:176830527-176830527 5:177403526-177403526
11 F12 , SLC34A1 NM_000505.3(F12):c.1272G>C (p.Thr424=)SNV Benign/Likely benign 352988 rs61737766 5:176830597-176830597 5:177403596-177403596
12 F12 , SLC34A1 NM_003052.5(SLC34A1):c.*361T>CSNV Benign/Likely benign 352983 rs539754545 5:176825648-176825648 5:177398647-177398647
13 F12 , SLC34A1 NM_003052.5(SLC34A1):c.1483C>T (p.Arg495Cys)SNV Benign/Likely benign 352973 rs199565633 5:176824850-176824850 5:177397849-177397849
14 F12 , SLC34A1 NM_003052.5(SLC34A1):c.1719A>G (p.Leu573=)SNV Benign/Likely benign 352976 rs148575220 5:176825086-176825086 5:177398085-177398085
15 F12 , SLC34A1 NM_000505.3(F12):c.1299C>T (p.Asn433=)SNV Benign/Likely benign 352987 rs17876033 5:176830570-176830570 5:177403569-177403569
16 F12 , SLC34A1 NM_000505.4(F12):c.1251-9C>TSNV Benign 256309 rs17876032 5:176830627-176830627 5:177403626-177403626
17 F12 , SLC34A1 NM_003052.5(SLC34A1):c.1635C>T (p.Gly545=)SNV Benign 352974 rs7379524 5:176825002-176825002 5:177398001-177398001
18 F12 , SLC34A1 NM_003052.5(SLC34A1):c.*202A>CSNV Benign 352980 rs6556319 5:176825489-176825489 5:177398488-177398488

Expression for Hereditary Angioedema

Search GEO for disease gene expression data for Hereditary Angioedema.

Pathways for Hereditary Angioedema

Pathways related to Hereditary Angioedema according to KEGG:

36
# Name Kegg Source Accession
1 Complement and coagulation cascades hsa04610

Pathways related to Hereditary Angioedema according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.13 SERPING1 SERPINA1 PLG KNG1 KLKB1 F12
2
Show member pathways
12.65 XPNPEP2 KNG1 KLKB1 KLK1 F12
3
Show member pathways
12.05 SERPING1 PLG KNG1 KLKB1 KLK1 F12
4
Show member pathways
11.96 MBL2 MASP2 MASP1 C4B C4A C1S
5
Show member pathways
11.9 SERPING1 MBL2 MASP2 MASP1 C4B C4A
6
Show member pathways
11.71 PLG KLKB1 ELANE
7
Show member pathways
11.66 KNG1 KLK1 BDKRB2 ACE
8
Show member pathways
11.64 MBL2 MASP2 MASP1 C4B C4A C1S
9 11.61 SERPING1 C4B C4A C1S
10 11.6 SERPING1 SERPINA1 PLG MBL2 MASP2 MASP1
11 11.48 PLG MBL2 MASP2 MASP1 C4B C4A
12 11.4 SERPING1 PLG KLKB1 F12
13 11.35 KLKB1 KLK1 F12
14 11.33 PLG KNG1 ELANE
15 10.87 PLG KLK1

GO Terms for Hereditary Angioedema

Cellular components related to Hereditary Angioedema according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 10.03 XPNPEP2 SERPING1 SERPINA1 PLG MASP2 KRT1
2 collagen-containing extracellular matrix GO:0062023 9.91 SERPING1 SERPINA1 PLG MBL2 KRT1 KNG1
3 extracellular region GO:0005576 9.91 XPNPEP2 SERPING1 SERPINA1 PLG MBL2 MASP2
4 blood microparticle GO:0072562 9.87 SERPING1 PLG KRT1 KNG1 C4B C4A
5 platelet alpha granule lumen GO:0031093 9.67 SERPING1 SERPINA1 PLG KNG1
6 extracellular space GO:0005615 9.55 SERPING1 SERPINA1 PLG MBL2 MASP2 MASP1

Biological processes related to Hereditary Angioedema according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 10.09 SERPING1 MBL2 MASP2 MASP1 C4B C4A
2 innate immune response GO:0045087 10.08 SERPING1 MBL2 MASP2 MASP1 F12 C4B
3 inflammatory response GO:0006954 9.97 KNG1 KLKB1 C4B C4A BDKRB2
4 blood coagulation GO:0007596 9.93 SERPING1 SERPINA1 PLG KNG1 KLKB1 F12
5 negative regulation of endopeptidase activity GO:0010951 9.91 SERPING1 SERPINA1 KNG1 C4B C4A
6 cellular protein metabolic process GO:0044267 9.9 SERPINA1 PLG KNG1 C4A
7 regulation of complement activation GO:0030449 9.89 SERPING1 CPN1 C4B C4A C1S
8 complement activation, classical pathway GO:0006958 9.88 SERPING1 MBL2 MASP2 C4B C4A C1S
9 platelet degranulation GO:0002576 9.86 SERPING1 SERPINA1 PLG KNG1
10 negative regulation of peptidase activity GO:0010466 9.78 SERPING1 SERPINA1 KNG1
11 extracellular matrix disassembly GO:0022617 9.76 PLG KLKB1 ELANE
12 complement activation GO:0006956 9.73 MBL2 MASP2 MASP1 C4B C4A C1S
13 zymogen activation GO:0031638 9.7 KLKB1 KLK1 F12
14 blood coagulation, intrinsic pathway GO:0007597 9.67 SERPING1 KNG1 KLKB1 F12
15 complement activation, lectin pathway GO:0001867 9.62 MBL2 MASP2 MASP1 KRT1
16 vasodilation GO:0042311 9.61 KNG1 BDKRB2
17 positive regulation of fibrinolysis GO:0051919 9.61 PLG KLKB1 F12
18 opsonization GO:0008228 9.59 MBL2 C4B
19 positive regulation of apoptotic cell clearance GO:2000427 9.57 C4B C4A
20 fibrinolysis GO:0042730 9.55 SERPING1 PLG KRT1 KLKB1 F12
21 Factor XII activation GO:0002542 9.54 KLKB1 F12
22 hemostasis GO:0007599 9.43 SERPING1 SERPINA1 PLG KNG1 KLKB1 F12
23 proteolysis GO:0006508 9.36 XPNPEP2 PLG MASP2 MASP1 KLKB1 KLK1

Molecular functions related to Hereditary Angioedema according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 10 XPNPEP2 PLG MASP2 MASP1 KLKB1 KLK1
2 serine-type endopeptidase activity GO:0004252 9.76 PLG MASP2 MASP1 KLKB1 KLK1 F12
3 peptidase inhibitor activity GO:0030414 9.63 SERPING1 SERPINA1 KNG1
4 protease binding GO:0002020 9.61 SERPINA1 ELANE BDKRB2
5 endopeptidase activity GO:0004175 9.58 PLG ELANE ACE
6 serine-type peptidase activity GO:0008236 9.56 PLG MASP2 MASP1 KLKB1 KLK1 F12
7 calcium-dependent protein binding GO:0048306 9.54 MBL2 MASP2 MASP1
8 endopeptidase inhibitor activity GO:0004866 9.5 KNG1 C4B C4A
9 peptidase activity GO:0008233 9.36 XPNPEP2 PLG MASP2 MASP1 KLKB1 KLK1

Sources for Hereditary Angioedema

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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